{"doi":"10.17615/1qs8-pe15","title":"SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract","abstract":"The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expres-sion in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-in-fected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings high-light the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host in-teractions in protective immunity, host susceptibility, and virus pathogenesis.","journal":"UNC Libraries","year":2020,"id":115996,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105509,"name":"Hong Dang","orcid":"0000-0002-7305-4208","position":1,"is_corresponding":false},{"id":105501,"name":"Takafumi Kato","orcid":"0000-0003-2248-3376","position":2,"is_corresponding":false},{"id":105111,"name":"Sarah R. Leist","orcid":"0000-0002-4989-5381","position":3,"is_corresponding":false},{"id":105519,"name":"Aravinda de Silva","orcid":null,"position":4,"is_corresponding":false},{"id":105516,"name":"Mark J. Cameron","orcid":"0000-0003-4768-4094","position":5,"is_corresponding":false},{"id":105529,"name":"Wanda K. O’Neal","orcid":"0000-0003-2412-5943","position":6,"is_corresponding":false},{"id":540773,"name":"David R. Martinez","orcid":"0000-0002-1689-5529","position":7,"is_corresponding":false},{"id":105499,"name":"Takanori Asakura","orcid":"0000-0003-3122-6937","position":8,"is_corresponding":false},{"id":105528,"name":"Ilona Jaspers","orcid":"0000-0001-8728-0305","position":9,"is_corresponding":false},{"id":105527,"name":"Adam J. Kimple","orcid":"0000-0003-1670-8401","position":10,"is_corresponding":false},{"id":104944,"name":"Longping V. Tse","orcid":"0000-0001-7582-8396","position":11,"is_corresponding":false},{"id":105503,"name":"Boyd L. Yount","orcid":"0000-0002-6099-8429","position":12,"is_corresponding":false},{"id":12178,"name":"Purushothama Rao Tata","orcid":"0000-0003-4837-0337","position":13,"is_corresponding":false},{"id":105507,"name":"Andrew J. Ghio","orcid":"0000-0003-0502-6448","position":14,"is_corresponding":false},{"id":542838,"name":"Gang Chen","orcid":"0000-0002-8320-6594","position":15,"is_corresponding":false},{"id":105524,"name":"Steven Salvatore","orcid":"0000-0001-7237-2696","position":16,"is_corresponding":false},{"id":105497,"name":"Caitlin E. Edwards","orcid":"0000-0003-4228-2192","position":17,"is_corresponding":false},{"id":5947,"name":"Yixuan J. Hou","orcid":"0000-0002-8323-7243","position":18,"is_corresponding":false},{"id":105520,"name":"David M. Margolis","orcid":"0000-0001-5714-0002","position":19,"is_corresponding":false},{"id":33125,"name":"Fernando J. Martínez","orcid":"0000-0002-2412-3182","position":20,"is_corresponding":false},{"id":542839,"name":"David J. Kelvin","orcid":"0000-0001-7757-9493","position":21,"is_corresponding":false},{"id":105521,"name":"Alena J. Markmann","orcid":"0000-0003-3656-9322","position":22,"is_corresponding":false},{"id":105502,"name":"Rhianna E. Lee","orcid":"0000-0003-2039-1304","position":23,"is_corresponding":false},{"id":105530,"name":"Richard C. Boucher","orcid":"0000-0002-5745-3989","position":24,"is_corresponding":false},{"id":105508,"name":"Lisa E. Gralinski","orcid":"0000-0003-1374-8002","position":25,"is_corresponding":false},{"id":105510,"name":"Rodney C. Gilmore","orcid":"0000-0002-3821-8422","position":26,"is_corresponding":false},{"id":105517,"name":"Cheryl Cameron","orcid":"0000-0002-0574-3781","position":27,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":28,"is_corresponding":false},{"id":105513,"name":"M. Leslie Fulcher","orcid":null,"position":29,"is_corresponding":false},{"id":105512,"name":"Ling Sun","orcid":"0000-0001-9040-4188","position":30,"is_corresponding":false},{"id":105500,"name":"Kenneth H. Dinnon","orcid":"0000-0002-8942-1551","position":31,"is_corresponding":false},{"id":105523,"name":"Ross E. Zumwalt","orcid":null,"position":32,"is_corresponding":false},{"id":105522,"name":"Luther A. Bartelt","orcid":"0000-0002-7596-4272","position":33,"is_corresponding":false},{"id":105504,"name":"Teresa Mascenik","orcid":"0000-0002-9694-756X","position":34,"is_corresponding":false},{"id":105515,"name":"Nathan I. Nicely","orcid":"0000-0002-0025-2377","position":35,"is_corresponding":false},{"id":105496,"name":"Kenichi Okuda","orcid":"0000-0001-9341-2730","position":36,"is_corresponding":false},{"id":105112,"name":"Alexandra Schäfer","orcid":null,"position":37,"is_corresponding":false},{"id":105506,"name":"Kenneth N. Olivier","orcid":null,"position":38,"is_corresponding":false},{"id":105526,"name":"Vishwaraj Sontake","orcid":"0000-0002-8532-7680","position":39,"is_corresponding":false},{"id":72632,"name":"Scott H. Randell","orcid":"0000-0001-5351-2841","position":40,"is_corresponding":false},{"id":105514,"name":"Alessandra Livraghi-Butrico","orcid":"0000-0001-8751-3631","position":41,"is_corresponding":false},{"id":105511,"name":"Satoko Nakano","orcid":"0000-0003-1708-3642","position":42,"is_corresponding":false},{"id":105525,"name":"Alain Borczuk","orcid":"0000-0001-6807-8064","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:40.596604Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}